Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Assembling cells into artificial 3-D microtissues, including a tiny gland

06.03.2009
Hybridized DNA is glue that sticks these cells together to resemble real tissue

As synthetic biologists cram more and more genes into microbes to make genetically engineered organisms produce ever more complex drugs and chemicals, two University of California chemists have gone a step further.

They have assembled different types of genetically engineered cells into synthetic microtissues that can perform functions such as secreting and responding to hormones, promising more complex biological capabilities than a single cell alone could produce.

"This is like another level of hierarchical complexity for synthetic biology," said coauthor Carolyn Bertozzi, UC Berkeley professor of chemistry and of molecular and cell biology and director of the Molecular Foundry at Lawrence Berkeley National Laboratory. "People used to think of the cell as the fundamental unit. But the truth is that there are collections of cells that can do things that no individual cell could ever be programmed to do. We are trying to achieve the properties of organs now, though not yet organisms."

While the synthetic tissues today comprise only a handful of cells, they could eventually be scaled up to make artificial organs that could help scientists understand the interactions among cells in the body and might some day substitute for human organs.

"We are really taking this into the third dimension now, which for me is particularly exciting," said first author Zev J. Gartner, a former UC Berkeley post-doctoral fellow who recently joined the UC San Francisco faculty as an assistant professor of pharmaceutical chemistry. "We are not simply linking cells together, we are linking them together in 3-D arrangements, which introduces a whole new level of cellular behavior which you would never see in 2-D environments."

Gartner and Bertozzi, the T.Z. and Irmgard Chu Distinguished Professor at UC Berkeley and a Howard Hughes Medical Institute investigator, report on their assembly of three-dimensional microtissues this week in the online early edition of the journal Proceedings of the National Academy of Sciences.

One type of cell that needs other cells to make it work properly is the stem cell, Bertozzi noted. Theoretically, using Gartner and Bertozzi's chemical technique, it should be possible to assemble stem cells with their helper cells into a functioning tissue that would make stem cells easier to study outside the body.

"In principal, we might be able to build a stem cell niche from scratch using our techniques, and then study those very well defined structures in controlled environments," Bertozzi said.

Bertozzi noted that most of the body's organs are a collection of many cell types that need to be in actual physical contact to operate properly. The pancreas, for example, is a collection of specialized cells, including insulin-secreting beta cells, that "sense glucose from the environment and respond by producing insulin. A complex feedback regulatory loop goes into all of this, and you need more than one cell type to achieve such regulation."

"If you really want to understand the way these cells behave in an organism, especially a human, you would like to recapitulate that environment as closely as possible in vitro," Gartner said. "We are trying to do that, with the aim that the rules we learn may help us control them better."

Gartner and Bertozzi assembled three types of cultured cells into onion-like layers by using two established technologies: DNA hybridization and Staudinger chemistry. DNA hybridization is like a "programmable glue," she said, that can stick cells together because of the highly precise nature of binding between complementary DNA strands: One strand of the DNA helix binds only to its complementary strand and nothing else. By putting a short DNA strand on the surface of one cell and its complementary strand on another cell, the researchers assure that the two lock together exclusively.

To get these specific DNA strands onto the cells, they used chemical reactions that do not interfere with cellular chemistry but nevertheless stick desired chemicals onto the cell surface. The technique for adding unusual but benign chemicals to cells was developed by Bertozzi more than a decade ago based on a chemical reaction called the Staudinger ligation.

After proving that they could assemble cells into microtissues, Gartner and Bertozzi constructed a minute gland – analogous to a lymph node, for example – such that one cell type secreted interleukin-3 and thereby kept a second cell type alive.

"What we did is build a little miniaturized, stripped-down system that operates on the same principle and looks like a miniaturized lymph node, an arrangement where two cells communicate with each another and one requires a signal from the other," she said. "The critical thing is that the two cells have to have a cell junction. If you just mix the cells randomly without connection, the system doesn't have the same properties."

She expects that eventually, clusters could be built on clusters to make artificial organs that someday may be implanted into humans.

"Our method allows the assembly of multicellular structures from the bottom up. In other words, we can control the neighbors of each individual cell in a mixed population," she said. "By this method, it may be possible to assemble tissues with more sophisticated properties."

One interesting aspect of the technique is that DNA hybridization seems to be temporary, like a suture. Eventually, the cells may substitute their own cell-cell adhesion molecules for the DNA, creating a well-knit and seemingly normal, biological system.

Robert Sanders | EurekAlert!
Further information:
http://www.berkeley.edu

More articles from Life Sciences:

nachricht Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz

nachricht Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Fighting drug resistant tuberculosis – InfectoGnostics meets MYCO-NET² partners in Peru

28.04.2017 | Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

 
Latest News

Wireless power can drive tiny electronic devices in the GI tract

28.04.2017 | Medical Engineering

Ice cave in Transylvania yields window into region's past

28.04.2017 | Earth Sciences

Nose2Brain – Better Therapy for Multiple Sclerosis

28.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>